Survival results according to Oncotype Dx recurrence score in patients with hormone receptor positive HER-2 negative early-stage breast cancer: first multicenter Oncotype Dx recurrence score survival data of Turkey.

Background: The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions. Patients and methods: Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS. Results: A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18. Conclusion: This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.

Teaching Culturally and Linguistically Diverse Students: Exploring the Challenges and Perceptions of Nursing Faculty.

AIM: The aim of this research was to analyze the challenges of nurse faculty when teaching culturally and linguistically diverse (CLD) students. BACKGROUND: CLD students struggle academically and may need accommodations to be successful. There is a lack of research on challenges faced by faculty when teaching CLD students and faculty perceptions of those challenges. METHOD: Data were collected via an online survey and in-person interviews. RESULTS: Several challenges were uncovered. The most common challenges were related to language barriers and lack of support in teaching CLD students. CONCLUSION: Nursing faculty members have several challenges in teaching CLD nursing students and should receive training to better understand, assess, and instruct their students.

Cost effectiveness of Gene Expression Profiling in Patients with Early-Stage Breast Cancer in a Middle-Income Country, Turkey: Results of a Prospective Multicenter Study.

OBJECTIVE: Breast cancer is a heterogenous disease, and genetic profiling helps to individualize adjuvant treatment. The Oncotype DX is a validated test to predict benefit of adjuvant systemic treatment. The aims of this study are to determine the costs of chemotherapy in government hospitals in Turkey and evaluate the cost-effectiveness of the Oncotype DX from the national insurance perspective. MATERIALS AND METHODS: A Markov model was developed to make long term projections of distant recurrence, survival, quality adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative or up to 3 node-positive early stage breast cancer. Turkish decision impact study patient data were captured for model reference. In that study, ten academic centers across Turkey participated in a prospective trial. Of 165 patients with pT1-3, pN0-N1mic, ER-positive, and HER-2 negative tumors, 57% had low recurrence score (RS), 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in chemotherapy treatment decisions following Oncotype DX was 33%. RESULTS: The cost of adjuvant chemotherapy in public hospitals was estimated at $3.649, and Oncotype Dx test was $5.141. Based on the cost-effectiveness analysis, Oncotype DX testing was estimated to improve life expectancy (+0.86 years) and quality-adjusted life expectancy (+0.68 QALYs) versus standard care. The incremental cost-effectiveness ratio (ICERs) of Oncotype DX was estimated to be $7207.9 per QALY gained and $5720.6 per LY gained versus current clinical practice. CONCLUSION: As Oncotype DX was found both cost-effective and life-saving from a national perspective, the test should be introduced to standard care in patients with ER+, HER-2 negative early-stage breast cancer in Turkey.

Impact of Oncotype DX Recurrence Score on Treatment Decisions: Results of a Prospective Multicenter Study in Turkey.

INTRODUCTION: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX(®) 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the impact of the Recurrence Score(®) (RS) on treatment decisions and physician perceptions in Turkey. We also studied correlations between RS and routine risk factors. PATIENTS AND METHODS: Ten academic centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at multidisciplinary tumor conferences. The initial treatment decision was recorded before tumor blocks were sent to the central laboratory. Each case was brought back to tumor conference after receiving the RS result. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classical risk factors were evaluated using univariate and multivariate analyses. RESULTS: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in treatment decision was 33%. Initially, chemotherapy followed by hormonal therapy (CT+HT) was recommended to 92 (56%) of all patients, which decreased to 61 (37%) patients post-RS assay (p<0.001). Multivariate analysis indicated that progesterone receptor (PR) and Ki-67 scores were significantly related to RS. CONCLUSION: Oncotype DX testing may provide meaningful additional information in carefully selected patients.

Correlations Between Oncotype DX Recurrence Score and Classic Risk Factors in Early Breast Cancer: Results of A Prospective Multicenter Study in Turkey.

OBJECTIVE: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the correlations between Recurrence Score (RS) and routine risk factors. MATERIALS AND METHODS: Ten academic centers across Turkey participated in this prospective trial. Consecutive patients with breast cancer who had pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at tumor conferences. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classic risk factors were evaluated using univariate and multivariate analyses. RESULTS: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of the 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. Multivariate analysis indicated that progesterone receptor (PR) and Ki67 scores were significantly related to RS. CONCLUSION: Oncotype DX Recurrence Score does not seem to have a significant correlation with the majority of classic risk factors, but it may have a correlation with PR score and Ki67 score.

Nine weeks versus 1 year adjuvant trastuzumab in patients with early breast cancer: an observational study by the Turkish Oncology Group (TOG).

BACKGROUND: Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey. METHODS: Records of 680 patients with HER2-positive early breast cancer who received adjuvant trastuzumab plus chemotherapy were obtained and patients were followed up to compare the disease-free survival (DFS) outcome of 9 weeks versus 1 year trastuzumab. RESULTS: Nine weeks and 1 year trastuzumab was given to 202 (29.7 %) and 478 (70.3 %) patients, respectively. There was a significantly lower rate of patients with negative lymph nodes in the 9-week trastuzumab group. At median 3 years of follow-up from the date of starting trastuzumab, the DFS rates were 88.6 and 85.6 %, respectively (p = 0.670). When adjusted for all the prognostic factors that were significant on univariate analysis, again there was no significant difference in DFS between the groups (HR 0.675; 95 % CI 0.370-1.231; p = 0.200). Cardiac toxicity defined as a ≥15 % decrease in LVEF was significantly higher in the 1-year trastuzumab group (1.88 % versus none for 1-year and 9-week trastuzumab groups, respectively; p = 0.050). CONCLUSION: The results of this observational study suggest that DFS outcome of 9 weeks of adjuvant trastuzumab may be comparable to 1 year adjuvant trastuzumab: this needs confirmation by randomized trials.

Impact of locoregional treatment on survival in patients presented with metastatic breast carcinoma.

OBJECTIVES: In this study, we tried to evaluate the efficacy of locoregional treatment (LRT) in patients with metastatic breast carcinoma (MBC). MATERIALS AND METHODS: The medical records of 227 patients with MBC at initial presentation between April 1999 and January 2013 were retrospectively evaluated. The median age at diagnosis was 50 years (range, 27-83 years). Thirty-nine patients (17%) had no LRT. Among patients who had LRT, 2 (1%) had locoregional radiotherapy (RT) alone, 54 (29%) had surgery alone [mastectomy, n = 50; breast conserving surgery (BCS), n = 4] and 132 (70%) had surgery (mastectomy, n = 119; BCS, n = 13) followed by locoregional RT. RESULTS: The median follow-up time was 35 months (range, 4-149 months). Five-year OS and PFS rates were 44% and 20%, respectively. In both univariate and multivariate analysis LRT per se did not affect OS and PFS rates. However, the 5-year OS and PFS rates were significantly higher in patients treated with locoregional RT than the ones who were not. The corresponding rates were 56% vs. 24% for OS and 27% vs. 7% for PFS (p < 0.001). Median survival was 67 months and 37 months, respectively. CONCLUSION: Our study showed that patients with MBC who received postoperative locoregional RT may have a survival advantage compared with patients who were only treated by surgery. A phase III trial testing the role of adjuvant locoregional RT may help to distinguish patients who will benefit from adjuvant RT.

Metaplastic breast carcinoma: a heterogeneous disease.

The aim of this study is to evaluate clinicopathologic characteristics and the multi-disciplinary treatment results of metaplastic breast cancer (MBC) patients treated in a single institute. Seventeen female patients with MBC treated in our department between June 2000 and January 2012 were identified and retrospectively evaluated. The median age at diagnosis was 46 years (range, 26-66 years). The median tumor size at diagnosis was 3.5 cm (range 1.5-12 cm). Six (35%) patients underwent breast conservation surgery and 11 (65%) mastectomy. Axillary lymph node metastasis was found in 6 (35%) patients. Twelve (71%) had triple negative tumors. Postoperative RT and systemic adjuvant treatment was given to all patients accordingly to stage and biological characteristics. Median follow-up time was 27 months (range, 12-151 months). At the time of this analysis, 14 (82%) patients were alive with no evidence of disease, and 1 (6%) was alive with disease. The 3-year OS was 91% and 5-year 80%, and DFS rates were 76% and 76%, respectively. Despite the young age of our patients with mostly high grade tumors, larger tumor size and higher rates of lymph node metastasis, the survival outcomes in our study are favorable in comparison with previously reported series.

The relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 and glutathione S transferase Pi polymorphisms.

The aim of this prospective clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 (CBR3p.V244M) and glutathione S transferase Pi (GSTP1p.I105V) polymorphisms. Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study. The patients' cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy, as well as 1 year following therapy. Gene polymorphisms were genotyped in 70 patients using TaqMan probes, validated by DNA sequencing. A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p.V244M polymorphism. Patients with G-allele carriers of GSTP1p.I105V polymorphism were common (60%), with significantly decreased PFR compared to patiens with AA genotype. Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters.

Acute transient encephalopathy after weekly paclitaxel infusion.

Paclitaxel is highly active against a variety of solid tumors including breast lung, ovarian and head and neck cancer. Although peripheral neurotoxicity is well-known side effect, central nervous system (CNS) toxicity-related standard dose of paclitaxel is extremely uncommon, because paclitaxel dose not cross the blood-brain barrier and is not detectable in the cerebrospinal fluid. We present a patient with advanced stage breast carcinoma who developed acute and spontaneous resolving encephalopathy after weekly dose of paclitaxel. The patient did not have brain metastasis, or prior whole-brain irradiation, or any type of neurosurgery. Radiological imaging studies showed no abnormalities. CNS toxicity of paclitaxel should be kept in mind in patients without a previous history of brain metastasis or brain irradiation and even with low weekly doses.

Increased mean corpuscular volume of erythrocytes during capecitabine treatment: a simple surrogate marker for clinical response.

AIMS AND BACKGROUND: Capecitabine, as all fluoropyrimidines, interferes with vitamin metabolism and may thus have an impact on hematopoiesis. It is metabolized to its active form 5-fluoruracil by the enzyme thymidine phosphorylase, which exists in higher concentrations in tumor tissue and liver than in normal tissues. In the study, we investigated the changes in mean corpuscular volume (MCV) of red blood cells and the possible correlation of these changes with the clinical outcome of capecitabine treatment in women with metastatic breast cancer. METHODS AND STUDY DESIGN: Data from 75 metastatic breast cancer patients were analyzed retrospectively. Capecitabine was used at a dose of 2500 mg/m² daily for 14 days of every 3-week period. Mean corpuscular volume of red blood cells and other parameters of complete blood count were recorded at the beginning of the treatment, in the ninth week, and periodically thereafter. RESULTS: Mean age was 51.5 ± 10.8 and 61.3% of the patients were premenopausal. Capecitabine was administered as the median 3rd line (min-max: 1-9) treatment and a median of 6 cycles (min-max: 1-24) for metastatic breast cancer. Median ΔMCV level (post-treatment values at ninth week - baseline) was 8. ΔMCV was ≥8 in 37 patients and <8 in 38 patients. The 35 of the 37 patients with ΔMCV level ≥8 and 25 of the 38 patients with ΔMCV level <8 had clinical benefit (complete response + partial response + stable disease) from capecitabine treatment (P = 0.02). However, the difference between progression-free survival of the patients with ΔMCV levels higher than 8 and those with ΔMCV levels lower than 8 according to Kaplan-Meier survival analysis was not statistically significant (6.7 and 4.3 months, respectively, P = 0.26). Additionally, median ΔMCV level was 9.1 (min-max: -2.4 to 24.9) among patients who had clinical benefit and 5.90 (min-max: -0.8 to 12.3) among nonresponders (P = 0.016). CONCLUSIONS: Capecitabine increases the mean corpuscular volume levels of red blood cells by a yet unidentified mechanism. Early increment of mean corpuscular volume levels is higher than 8, i.e. by the 9th week, might predict clinical benefit from the treatment.

Characteristics of breast cancer patients with central nervous system metastases: a single-center experience.

The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

Wwox and Ap2gamma expression levels predict tamoxifen response.

PURPOSE: Assessment of expression levels of Wwox, Wwox-interacting proteins Ap2alpha, Ap2gamma, and ErbB4, the Ap2gamma transcriptional target protein Her2, and the possible Ap2alpha transcriptional target PrkaRIalpha, in breast cancers, to determine their roles in tamoxifen resistance. The hypothesis was that sequestration of Wwox interactors in the cytoplasm might control tamoxifen response. EXPERIMENTAL DESIGN: Tissue sections from 51 tamoxifen-sensitive and 38 tamoxifen-resistant, estrogen receptor alpha-positive breast cancers were stained for the above proteins, as well as progesterone receptor (PR). The relation of tamoxifen resistance and other clinical features, with level of expression of these proteins, and pairwise correlations among various immunohistochemical markers were determined. RESULTS: Menopausal status, tumor, node, and stage, loss of PR, lost or reduced expression of Wwox, and high level of expression of PrkaRIalpha, Ap2gamma, and Her2 were significantly correlated with tamoxifen resistance. In multivariate analysis, Wwox, PrkaRIalpha, Ap2gamma, and ErbB4 were found to be independent markers of tamoxifen resistance. Reduced Wwox expression was better than PR in prediction of resistance, especially in high-risk patients, and nuclear Ap2gamma expression was better than Her2, especially in low-risk patients. CONCLUSION: The results illustrate the complex relationships among the marker proteins assessed in this in vivo study and suggest new markers for prediction of response to tamoxifen treatment as well as possible new targets for treatment of breast cancer. Wwox and Ap2gamma emerge as new biomarkers that may be superior to PR and Her2 in predicting tamoxifen response.

Endobronchial metastasis of thyroid follicular carcinoma.

Well-differentiated forms of thyroid cancer, including follicular carcinoma, usually have good prognoses. But they are also known to metastasize to the bones, lungs and central nervous system. Endobronchial metastasis is exceptionally rare. In this paper, we report on a patient with endobronchial metastasis of follicular thyroid carcinoma. A 77-year-old male patient presented to our hospital with hemoptysis and a growing mass over the right clavicula. Computerized tomography (CT) of the chest revealed multiple lung metastases. Flexible bronchoscopy revealed a fragile polypoid mass of 1.5 cm, 6 cm distal to the vocal cords. Biopsy from the supraclavicular mass was consistent with follicular thyroid carcinoma. Taking into account the advanced nature of the disease as well as the general condition and age of the patient, aggressive treatment modalities were not considered in the management. Palliation for hemoptysis was attained by external radiotherapy. After radiotherapy, hemoptysis did not recur, and the patient was discharged. Although endobronchial metastasis of thyroid follicular carcinoma is very rare, the presence of endobronchial metastasis may be life threatening due to massive hemoptysis, and such a lesion must be suspected in any cancer patients presenting with hemoptysis.

Expression of PTEN, cyclin D1, P27/KIP1 in invasive ductal carcinomas of the breast and correlation with clinicopathological parameters.

In this study, tumour tissue samples of 85 primary breast cancer patients were evaluated for phosphatase and tensin homolog deleted on chromosome ten (PTEN), cyclin D1 and P27/Kip1 expression patterns. The results were correlated with clinicopathological parameters. Loss of PTEN protein expression was present in 32.5% of the cases. Cyclin D1 was overexpressed in 54.2% and P27/Kip1 in 89.3% of the cases. Statistically significant associations were found between PTEN and cyclin D1 expression patterns, and cyclin D1 expression and tumour size.

Capecitabine-induced severe hypertriglyceridemia: report of two cases.

OBJECTIVE: To report 2 cases of severe hypertriglyceridemia associated with the use of oral capecitabine. CASE SUMMARIES: The first patient was a 73-year-old woman with metastatic breast carcinoma who received capecitabine 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 324 mg/dL; after 2 cycles of capecitabine, levels increased to 916 mg/dL. Although lipid-lowering treatment was initiated, triglyceride levels peaked at 1782 mg/dL by the end of the seventh cycle. Eight weeks after capecitabine treatment was stopped, triglyceride levels decreased to 118 mg/dL. The second patient was a 59-year-old man with metastatic colorectal carcinoma who was placed on capecitabine treatment at a dosage of 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 244 mg/dL; levels peaked at 1455 mg/dL at the end of the fifth cycle. Capecitabine treatment was discontinued due to disease progression, and triglyceride levels decreased to 154 mg/dL after 11 weeks. DISCUSSION: The most frequently reported adverse effects of capecitabine are gastrointestinal and hematologic effects and palmar-plantar erythrodysesthesia. Drug-induced hyperlipidemia may appear more readily in individuals with hereditary lipoprotein lipase deficiency because decreased lipoprotein lipase activity might make these individuals more susceptible to a rise in triglyceride levels. The Naranjo probability scale indicated a probable relationship between capecitabine and severe hypertriglyceridemia. CONCLUSIONS: Capecitabine should be prescribed with care, especially in patients with preexisting hypertriglyceridemia. The question of whether capecitabine actually causes hypertriglyceridemia needs careful consideration, and the possible mechanism by which it may cause this adverse effect requires further investigation.